Understanding the workings of stem cells is now seen as essential to the progress of regenerative medicine, tissue engineering and cancer therapeutics. Recently, there has been a growing awareness that the behaviors of stem cells emerge out of the highly complex interactions of dynamic networks of gene regulation and proliferative control. The need to describe, predict, and ultimately understand such interactions is drawing ideas and investigators from the field of systems biology into stem cell biology.
The last few years have seen significant advances in our understanding of the molecular mechanisms of stem-cell-fate specification. New and emerging high-throughput techniques, as well as increasingly accurate loss-of-function perturbation techniques, are allowing us to dissect the interplay among genetic, epigenetic, proteomic, and signaling mechanisms in stem-cell-fate determination with ever-increasing fidelity.
Taken together, recent reports using these new techniques demonstrate that stem-cell-fate specification is an extremely complex process, regulated by multiple mutually interacting molecular mechanisms involving multiple regulatory feedback loops. Given this complexity and the sensitive dependence of stem cell differentiation on signaling cues from the extracellular environment, how are we best to develop a coherent quantitative understanding of stem cell fate at the systems level? One approach that we and other researchers have begun to investigate is the application of techniques derived in the computational disciplines (mathematics, physics, computer science, etc.) to problems in stem cell biology.
Systems biology emerged around 2000, along with microarrays and other high-throughput techniques that can collect hard drives full of quantitative biological data. By using data to build simulations of biological phenomena, the goal is to create hypotheses and ‘intuition’ beyond that of a single human brain. Not only does the analysis of all this data require a mathematical framework and computational tools, but it presents interesting questions for theoreticians with applied mathematics, computer science or engineering backgrounds.
How does a stem cell decide what specialized identity to adopt – or simply to remain a stem cell? A new study suggests that the conventional view, which assumes that cells are “instructed” to progress along prescribed signaling pathways, is too simplistic. Instead, it supports the idea that cells differentiate through the collective behavior of multiple genes in a network that ultimately leads to just a few endpoints – just as a marble on a hilltop can travel a nearly infinite number of downward paths, only to arrive in the same valley.
The findings, published in the May 22 issue of Nature, give a glimpse into how that collective behavior works, and show that cell populations maintain a built-in variability that nature can harness for change under the right conditions. The findings also help explain why the process of differentiating stem cells into specific lineages in the laboratory has been highly inefficient.
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Clin Transl Sci. 2009 Jun;2(3):222-7.
The pandemic of chronic degenerative diseases associated with aging demographics mandates development of effective approaches for tissue repair. As diverse stem cells directly contribute to innate healing, the capacity for de novo tissue reconstruction harbors a promising role for regenerative medicine. Indeed, a spectrum of natural stem cell sources ranging from embryonic to adult progenitors has been recently identified with unique characteristics for regeneration. The accessibility and applicability of the regenerative armamentarium has been further expanded with stem cells engineered by nuclear reprogramming. Through strategies of replacement to implant functional tissues, regeneration to transplant progenitor cells or rejuvenation to activate endogenous self-repair mechanisms, the overarching goal of regenerative medicine is to translate stem cell platforms into practice and achieve cures for diseases limited to palliative interventions. Harnessing the full potential of each platform will optimize matching stem cell-based biologics with the disease-specific niche environment of individual patients to maximize the quality of long-term management, while minimizing the needs for adjunctive therapy. Emerging discovery science with feedback from clinical translation is therefore poised to transform medicine offering safe and effective stem cell biotherapeutics to enable personalized solutions for incurable diseases.
Stem cells platforms Properties Embryonic Author: dragon web profit

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Regenerative medicine, propelled by the recent progress made in transplant medicine, stem cell biology, and related biomedical fields, is primed to expand the therapeutic armamentarium available in the clinical setting, and thereby, ameliorate disease outcome while reducing the burden of chronic therapy. This progress offers a transformative paradigm with curative objectives and goals to address disease management demands unmet by traditional (pharmaco)therapy. In particular, stem cell-based regenerative medicine is poised to drive the evolution of medical sciences from traditional palliation, which mitigates symptoms, to curative therapy aimed at treating the disease cause.
Stem cells have a unique aptitude to differentiate into specialized cell types and form new tissue, thus providing the active ingredient of regenerative therapy. Guided by the increasingly understood principles of molecular embryology, stem cell biology has transformed the understanding of tissue and organ formation and has contributed to the decoding of mechanisms underlying tissue homeostasis and repair. Strategies to promote, augment, and re-establish developmental processes utilized in natural embryogenesis are at the core of translating the science of stem cell biology into the practice of regenerative medicine.
Specialized application of therapeutic repair starts with the use of standardized stem cell-based platforms such as the increasingly established embryonic, perinatal, and adult stem cell sources and their cell progeny derivatives. Embryonic stem cells have the advantage of an unequaled pluripotent differentiation plasticity associated with a robust repair capacity, yet access for clinical applications remains a significant limitation, along with a risk of uncontrolled growth and immunological intolerance. While methods for lineage restriction are increasingly developed and validated, the adult stem cells—hematopoietic or mesenchymal in origin—have the benefit of autologous immunologic status and are readily available for clinical applications, although the induction of reliable tissue-specific differentiation remains a possible limitation. Perinatal stem cells incorporate advantageous characteristics from both embryonic and adult stem cells, including potential autologous status and broader differentiation capacity than adult stem cells, and provide the most available stem cell source when harvested at birth.
Alternatively, bioengineered platforms, including therapeutic cloning and nuclear reprogramming, further offer generation of hybrid cells and tissues. In this context, enabling biotechnology platforms have most recently emerged to create hybridized stem cell types designed to systematically address cell characteristics that currently limit the clinical translation of more standard cell-based therapeutics. Exploiting genetic and epigenetic factors to regulate phenotypic outcomes, the biotechnology platforms achieve guided genetic reprogramming of adult cells back to an embryonic-like state (induced pluripotent stem cell). These platforms bypass the need for embryo extraction to generate categorical pluripotent stem cell phenotypes and recycle somatic nuclei to form autologous, immunotolerant cell-based products. Reprogramming of the adult stem cells to generate customized embryonic-like stem cells offers, thereby, an attractive tool to engineer patient-specific regenerative therapies.
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Description of tissue regeneration may date back to the Greek mythology, where Prometheus is punished by Zeus for stealing from Mount Olympus the sacred fire for humankind. The myth describes a vulture that feasts from an open wound in the liver, yet the liver renews daily, demonstrating a unique capacity to regenerate. The concept of regeneration is commonly observed, but often unappreciated in daily medical practice. The rapid healing of skin cuts and abrasions exemplifies natural repair processes in which new tissue formation is derived from multiple stem cell populations, including epidermal, mesenchymal, neural crest-derived, and circulating stem cells. The capacity for regeneration is particularly evident in the young, in comparison to those with degenerative diseases or the elderly who typically are stress intolerant. Repair mechanisms remain, however, active even in advanced senescence as elderly patients can heal well after major surgical injuries. This active, self-reparative process of regeneration throughout the lifespan establishes the essential elements for the maintenance of tissue homeostasis and serves as the basis for the emerging field of therapeutic repair and stem cell-based regenerative medicine.
The evolution of pharmacotherapy toward reparative paradigms exploits the growing understanding of disease pathways and natural repair mechanisms to discover, validate, and ultimately, apply stem cell therapeutics targeted to the cause of disease. The multidisciplinary and complementary sciences of molecular medicine, bioengineering, and network biology have catalyzed the growth of stem cell applications. Tailored to the genetic and molecular profile of the individual patient, regenerative medicine integrates stem cell biology with personalized therapeutic, diagnostic, prognostic, and preventive solutions across human diseases, providing a cornerstone of modern individualized medicine practice
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Stem cell treatments have the potential to change the face of human disease and alleviate suffering. The ability of stem cells to self-renew and give rise to subsequent generations that can differentiate offers a large potential to culture tissues that can replace diseased and damaged tissues in the body, without the risk of rejection and side effects.
A number of stem cell treatments exist, although most are still experimental and/or costly, with the notable exception of bone marrow transplantation. Medical researchers anticipate one day being able to use technologies derived from adult and embryonic stem cell research to treat cancer, Type 1 diabetes mellitus, Parkinson’s disease, Huntington’s disease,Celiac Disease, cardiac failure, muscle damage and neurological disorders, along with many others.
1. Brain damage
Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. Healthy adult brains contain neural stem cells which divide and to maintain general stem cell numbers, or become progenitor cells. In the case of brain injury, although the reparative process appears to initiate, substantial recovery is rarely observed in adults, suggesting a lack of robustness.
Stem cells may also be used to treat brain degeneration, such as in Parkinson’s and Alzheimer’s disease.
2. Cancer
Research injecting neural (adult) stem cells into the brains of dogs has shown to be very successful in treating cancerous tumors. With traditional techniques brain cancer is almost impossible to treat because it spreads so rapidly. Researchers at the Harvard Medical School induced intracranial tumours in rodents. Then, they injected human neural stem cells. Within days the cells had migrated into the cancerous area and produced cytosine deaminase, an enzyme that converts a non-toxic pro-drug into a chemotheraputic agent. As a result, the injected substance was able to reduce tumor mass by 81 percent. The stem cells neither differentiated nor turned tumorigenic. Some researchers believe that the key to finding a cure for cancer is to inhibit cancer stem cells, where the cancer tumor originates. Currently, cancer treatments are designed to kill all cancer cells, but through this method, researchers would be able to develop drugs to specifically target these stem cells.
3. Spinal cord injury
A team of Korean researchers reported on November 25, 2003, that they had transplanted multipotent adult stem cells from umbilical cord blood to a patient suffering from a spinal cord injury and that she can now walk on her own, without difficulty. The patient had not been able to stand up for roughly 19 years. For the unprecedented clinical test, the scientists isolated adult stem cells from umbilical cord blood and then injected them into the damaged part of the spinal cord.
According to the October 7, 2005 issue of The Week, University of California researchers injected human embryonic stem cells into paralyzed mice, which resulted in the mice regaining the ability to move and walk four months later. The researchers discovered upon dissecting the mice that the stem cells regenerated not only the neurons, but also the cells of the myelin sheath, a layer of cells which insulates neural impulses and speeds them up, facilitating communication with the brain (damage to which is often the cause of neurological injury in humans).
In January 2005, researchers at the University of Wisconsin–Madison differentiated human blastocyst stem cells into neural stem cells, then into the beginnings of motor neurons, and finally into spinal motor neuron cells, the cell type that, in the human body, transmits messages from the brain to the spinal cord. The newly generated motor neurons exhibited electrical activity, the signature action of neurons. Transforming blastocyst stem cells into motor neurons had eluded researchers for decades. The next step will be to test if the newly generated neurons can communicate with other cells when transplanted into a living animal. Su-Chun said their trial-and-error study helped them learn how motor neuron cells, which are key to the nervous system, develop in the first place. The new cells could be used to treat diseases like Lou Gehrig’s disease, muscular dystrophy, and spinal cord injuries.
4. Heart damage
Several clinical trials targeting heart disease have shown that adult stem cell therapy is safe and effective, and is equally efficient in old as well as recent infarcts. Adult stem cell therapy for heart disease was commercially available on at least five continents at the last count (2007).
Possible mechanisms are:
Generation of heart muscle cells Stimulation of growth of new blood vessels that repopulate the heart tissue Secretion of growth factors, rather than actually incorporating into the heart Assistance via some other mechanism
It may be possible to have adult bone marrow cells differentiate into heart muscle cells.
5. Baldness
Hair follicles also contain stem cells, and some researchers predict research on these follicle stem cells may lead to successes in treating baldness through "hair multiplication", also known as "hair cloning". This treatment is expected to work through taking stem cells from existing follicles, multiplying them in cultures, and implanting the new follicles into the scalp. Later treatments may be able to simply signal follicle stem cells to give off chemical signals to nearby follicle cells which have shrunk during the aging process, which in turn respond to these signals by regenerating and once again making healthy hair.
6. Missing teeth
In 2004, scientists at King’s College London discovered a way to cultivate a complete tooth in mice and were able to grow them stand-alone in the laboratory. Researchers are confident that this technology can be used to grow live teeth in human patients.
In theory, stem cells taken from the patient could be coaxed in the lab into turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, which would be expected to take two months to grow. It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth.
Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.
7. Deafness
There has been success in re-growing cochlea hair cells with the use of stem cells.
8. Blindness and vision impairment
Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. Using embryonic stem cells, scientists are able to grow a thin sheet of totipotent stem cells in the laboratory. When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restoring vision. The latest such development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Dr. Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.
In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea of Deborah Catlyn, a woman who was blinded in one eye when an acid was thrown in her eye at a nightclub. The cornea, which is the transparent window of the eye, is a particularly suitable site for transplants. In fact, the first successful human transplant was a cornea transplant. The cornea has the remarkable property that it does not contain any blood vessels, making it relatively easy to transplant. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.
The University Hospital of New Jersey claims a success rate growing the new cells from transplanted stem cells varies from 25 percent to 70 percent.
In 2009, researchers at the University of Pittsburgh Medical center demonstrated that stem cells collected from human corneas can restore transparency without provoking a rejection response in mice with corneal damage.
In May of 2010, researchers at UC Irvine were able to successfully a grow a retina from stem cells.
9. Amyotrophic lateral sclerosis
Stem cells have cured rats with an Amyotrophic lateral sclerosis-like disease. The rats were injected with a virus to kill the spinal cord motor nerves related to leg movement, succeeded by injections of stem cells into their spinal cords. These migrated (passed through many layers of tissues) to the sites of injury where they were able to regenerate the dead nerve cells restoring the rats which were once again able to walk.
10. Graft vs. host disease and Crohn’s disease
Phase III clinical trials expected to end in second-quarter 2008 were conducted by Osiris Therapeutics using their in-development product Prochymal, derived from adult bone marrow. The target disorders of this therapeutic are graft-versus-host disease and Crohn’s disease.
11. Neural and behavioral birth defects
A team of researchers led by Prof. Joseph Yanai were able to reverse learning deficits in the offspring of pregnant mice who were exposed to heroin and the pesticide organophosphate. This was done by direct neural stem cell transplantation into the brains of the offspring. The recovery was almost 100 percent, as proved in behavioral tests in which the treated animals improved to normal behavior and learning scores after the transplantation. On the molecular level, brain chemistry of the treated animals was also restored to normal. Through the work, which was supported by the US National Institutes of Health, the US-Israel Binational Science Foundation and the Israel anti-drug authorities, the researchers discovered that the stem cells worked even in cases where most of the cells died out in the host brain.
The scientists found that before they die the neural stem cells succeed in inducing the host brain to produce large numbers of stem cells which repair the damage. These findings, which answered a major question in the stem cell research community, were published earlier this year in the leading journal, Molecular Psychiatry. Scientists are now developing procedures to administer the neural stem cells in the least invasive way possible – probably via blood vessels, making therapy practical and clinically feasible. Researchers also plan to work on developing methods to take cells from the patient’s own body, turn them into stem cells, and then transplant them back into the patient’s blood via the blood stream. Aside from decreasing the chances of immunological rejection, the approach will also eliminate the controversial ethical issues involved in the use of stem cells from human embryos.
12. Diabetes
Diabetes patients lose the function of their insulin-producing beta cells of their pancreas. Human embryonic stem cells may be grown in cell culture and stimulated to form insulin-producing cells that can be transplanted into the patient.
However, success depends on developing procedures in all required steps:[3]
    * Have the cells proliferate and generate sufficient amount of tissue     * Differentiation into the right cell type     * Survival of the cells in the recipient (prevention of transplant rejection)     * Integration with the surrounding tissue in the body     * Function appropriately in long-term
13. Orthopaedics
Clinical case reports in the treatment of orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased cartilage and meniscus volume in individual human subjects. The results of trials including more patients are yet to be published making it hard to extrapolate the generalizability of these case reports. A newly published safety study published by the same group shows good safety and less complications than surgical care in a large study group of 227 patients over a 3-4 year period.
Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects
14. Wound healing
In one experimental method in regenerative medicine, stem cells are used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells. A possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation. Researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration.
15. Infertility
Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis.
Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed. It could potentially treat azoospermia.
Author: dragon web profit

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Progress in stem cell biology has been accelerated through the integration of the fundamental fields of molecular embryology and immunology with the emerging multidisciplinary fields of systems biology, bioengineering, and disease networks. The translation into the clinical applications of regenerative medicine is guided by the opportunities of individualized disease management exploiting personalized prediction, diagnosis, prognosis, prevention, and ultimately, therapy tailored to the specific needs of each patient.


Author: dragon web profit

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Regenerative Medicine is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects. This field holds the promise of regenerating damaged tissues and organs in the body by stimulating previously irreparable organs to heal themselves. Regenerative medicine also empowers scientists to grow tissues and organs in the laboratory and safely implant them when the body cannot heal itself. Importantly, regenerative medicine has the potential to solve the problem of the shortage of organs available for donation compared to the number of patients that require life-saving organ transplantation, as well as solve the problem of organ transplant rejection, since the organ’s cells will match that of the patient.
Scientific research is working to make treatments available for clinical use. Treatments include both in vivo and in vitro procedures. In vivo meaning studies and trials performed inside the living body in order to stimulate previously irreparable organs to heal themselves. In vito treatments are applied to the body through implantation of a therapy studied inside the laboratory.
Anti-aging regenerative medicine refers to a group of biomedial approches to clinical therapies that may involve the use of stem cells. Examples include; the injection of stem cells or progenitor cells (cell therapies); another the induction of regeneration by biologically active molecules; and a third is transplantation of in vitro grown organs and tissues (tissue engineering).
There are four concentrations in the field of regenerative medicine:
1. Laboratory-grown organ transplant — create new body parts via therapeutic cloning (via somatic cell nuclear transfer).
2. cell therapy — There are two ideas behind the use of cells as a medical treatment. The first is to provide a source of missing cells, say to heal a tissue that is injured or to renew a population of cells that are killed off by a disease such as Alzheimer’s. The second notion is to manipulate cells to produce a missing substance, such as the protein that is missing in boys affected by Duchenne muscular dystrophy. Adult stem cells, which exist in all of us as a repair mechanism for tissues lost to trauma, disease, and wear and tear, have been studied for decades, and are already widely used to treat some conditions, such as leukemia.
3. Tissue engineering and biomaterials –The term "tissue engineering" refers to methods that promote the regrowth of cells lost to trauma or disease. Tissue engineers use many methods, including the manipulation of artificial and natural materials that provide structure and biochemical instructions to young cells as they grow into specific kinds of tissue. These materials/biomaterials are called scaffolds because they provide support and materials for tissue regrowth.
4. Medical device and artificial organ– An artificial organ is a man-made device that is implanted into, or integrated onto, a human to replace a natural organ, for the purpose of restoring a specific function or a group of related functions so the patient may return to as normal a life as possible. The replaced function doesn’t necessarily have to be related to life support, but often is. Implied by this definition is the fact that the device must not be continuously tethered to a stationary power supply, or other stationary resources, such as filters or chemical processing units. Periodic rapid recharging of batteries, refilling of chemicals, and/or cleaning/replacing of filters, would exclude a device from being called an artificial organ.
Artificial bladders represent a unique success in that these are autologous laboratory-grown living replacements (from a small sample of the patients’ own bladder tissue) known as bioartificial organ via tissue engineering technologies, as opposed to most other artificial organs which depend upon electro-mechanical contrivances, and may or may not incorporate any living tissue.
5. Clinical Translation — Clinical translation puts promising therapies into active trials.
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Regenerative medicine is a type of medical care to regenerate cells, tissues, or organs degeneration or loss after aging, accidents, or diseases and restore body functions. The idea of regeneration in medical care has a long history. In a broad sense, regenerative medicine includes rehabilitation or training for recovery of physical functions; the use of artificial hands, legs, and joints made from synthetic materials; and living cell transplantation such as skin transplantation, bone marrow transplantation, and organ transplantation.
When organs have been damaged, for instance, the mainstream approach was to detect the damaged organ as soon as possible and slow the progression by drug therapy or surgery. With medical advances, regenerative medicine is now applied to therapy in the form of organ transplantation. However, organ transplantation poses the challenging problems of lack of organ donors, rejection after organ transplantation, and ethical issues of transplantation of another person’s organs. High expectations have been placed on further advances in regenerative medicine, which has been studied worldwide as state-of-the-art medicine to solve these problems.
There are different types of regenerative medicine, one of which is stem cell transplantation. Stem cells have been extensively studied along with the recent developments in culture technology, molecular biology, tissue engineering, and genetic engineering, and stem cell-based regenerative medicine now draws attention as a national project. Stem cells have the ability to grow into specific cells and renew themselves in an undifferentiated state for a long time. In other words, stem cells are master cells that grow into tissues or organs. The use of the patient’s own cells to regenerate tissues or organs and restore function will overcome immunological rejection and ethical problems.

Regenerative medicine appears to be a medical treatment of unlimited potential, which maximizes the innate regenerative ability of the body. Potential treatments in regenerative medicine
Taken collectively, the advancements offered by anti-aging and regenerative medicine to improve the quality of, and/or extend the length of, the human lifespan, are the singlemost potent emerging biomedical technologies today.
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Parthenogenesis is a form of asexual reproduction found in females, where growth and development of embryos occurs without fertilization by a male. In plants, parthenogenesis means development of an embryo from an unfertilized egg cell, and is a component process of apomixis. The offspring produced by parthenogenesis are always female in species that use the XY sex-determination system, and male in those that use the ZW sex-determination system. Parthenogenesis (<Gr. "virgin birth") is production of offspring by a female with no genetic contribution from a male and without meiotic chromosome reduction. The process is common reproductive strategy among insects such as aphids, flies, ants, and honeybees, but is also known to occur in vertebrates including lizards, snakes, fish, birds, and amphibians.
The first demonstration of artificially-stimulated parthenogenesis in vitro was made by Jacques Loeb (1899), who was able to activate oocytes from sea urchins and frogs by pricking them with a needle or by changing the ambient salt concentration. Pincus (1939) demonstrated parthenogenetic activation of mammalian eggs using temperature and chemical stimuli. Thus far, parthenogenetic activation of eggs has been studied in a variety of mammals including mice, goats, cows, monkeys, and humans. Plachot et al. described parthenogenesis in humans by examining 800 human oocytes and showed that 12 activated parthenogenetically and four underwent normal cleavage. Although there have been no reports of naturally-occurring human parthenotes, a human parthenogenetic chimera has been described. The juvenile patient presented with developmental delay, apparent sex reversal, and entirely parthenogenetic blood leukocytes. This finding confirmed the viability of chimeras in higher mammals as presaged by successful murine experiments over the previous two decades
Both therapeutic cloning (nucleus from a donor cell is transferred into an enucleated oocyte), and parthenogenesis (oocyte is activated and stimulated to divide), permit extraction of pluripotent embryonic stem cells, and offer a potentially limitless source of cells for tissue engineering applications.
There is no confirmed example of de novo mammalian parthenogenetic reproduction, but mammalian oocytes can be artificially induced to undergo parthenogenesis in vitro by a two-step protocol involving electroporation and/or treatment with a chemical agent (ionomycin, ethanol, or inositol 1,4,5-triphosphate) to elevate Ca2+ levels transiently, followed by application of an inhibitor of protein synthesis (cycloheximide) or protein phosphorylation (6-dimethylaminopurine). Success rates and viability appear to be organism dependent. Mouse parthenotes are capable of developing beyond the post-implantation stage in vivo; porcine parthenotes have developed up to post-activation day 29 (limb bud stage, past the early heart beating stage); rabbit parthenotes until day 10–11; primates (Callithrix jacchus) have only been shown to implant. The reason for this arrested development is believed to be due to genetic imprinting. In normal zygotes maternal and paternal haploid genomes are epigenetically distinct, and both sets are required for successful development. Indeed, unstable chromosome modifications in the form of DNA methylation or histone modification are distinctly different in human sperm, compared to eggs. Therefore each gamete carries unique patterns of gene expression into the embryo. Since all genetic material in parthenotes is of maternal origin, there is no paternal imprinting component and this prevents proper development of extraembryonic tissues whose expression is regulated by the male genome. In most mammals – including primates – oocytes are arrested at metaphase II just before ovulation. Cytogenetic microscopy shows the presence of a 2n polar body under the zona pellucida and a 2n protonucleus in the cytoplasm. After chemical activation to mimic the effects of sperm penetration on changes in cellular Ca2+ gradient, the cell fails to complete meiosis II. Instead, the second polar body is never extruded, resulting in a diploid protonucleus derived from two sets of sister chromatids. These chromatids then begin to undergo mitosis resulting in a parthenote manifesting uniparental disomy.
Although the derivation of embryonic-like stem cells from oocytes (parthenogenetic stem cells, PSC) is relatively inefficient (perhaps due to complexities of genomic imprinting), when they are differentiated into adult tissues, they appear fully functional.
In spite of non-viability of monkey parthenotes, the extracted stem cells seem to assume the morphology and functional behavior of HESC and express appropriate ESC markers. They have embryonic-like replicative ability and have been propagated in vitro in an undifferentiated state for up to 14 months. In vitro, they have been differentiated into cardiomyocyte-like cells, smooth muscle, beating ciliated epithelia, adipocytes, several types of epithelial cells, as well as dopaminergic and serotoninergic neurons. Almost all of these neurons express TUJ1 (beta-tubulin III), and up to 25% of the TUJ1+ cells co-express tyrosine-hydroxylase. This latter enzyme marker is considered diagnostic for catecholaminergic neurons (dopamine, norepinephrine, and epinephrine. Furthermore, HPLC analysis of culture media following a depolarizing KCl-buffer identifies the release of the neurotransmitters dopamine and serotonin from the cells. Ater two weeks of differentiation, about half of the cells demonstrate neuronal morphology and begin to express voltage-dependent sodium channels that can be blocked by tetrodotoxin.
These observations are recapitulated in vivo, since injection of monkey PSC into immunocompromised mice induces formation of benign teratomas containing tissue derivatives from all three germ layers (ectoderm, endoderm and mesoderm) including cartilage, muscle, bone, neurons, skin, hair follicles, and intestinal epithelia. Of particular note is the apparent tendency of these cells to differentiate into neuronal tissues, as has been noted by chimera studies. The reasons for this underlying preference are not well understood although one possible explanation is that it is a consequence of purely maternal genomic imprinting, reflecting a lack of epigenetic balance that would be conferred by paternally-imprinted genes.
To be sure, parthenotes are not free from ethical controversy and are viewed by some in society as artificial entities that in some sense represent ‘tampering with nature.’ Since a parthenote is analogous to a mature ovarian teratoma (a spontaneous in vivo tumorigenic event) the de facto acceptance of experiments using teratoma tumor tissue lends some legitimacy to experimentation on parthenotes. These contradictions await reconciliation in a comprehensive ethical framework.
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Reprod Biol Endocrinol. 2003; 1: 102.
William L Fodor
The field of Regenerative Biology as it applies to Regenerative Medicine is an increasingly expanding area of research with hopes of providing therapeutic treatments for diseases and/or injuries that conventional medicines and even new biologic drug therapies cannot effectively treat. Extensive research in the area of Regenerative Medicine is focused on the development of cells, tissues and organs for the purpose of restoring function through transplantation. The general belief is that replacement, repair and restoration of function is best accomplished by cells, tissues or organs that can perform the appropriate physiologic/metabolic duties better than any mechanical device, recombinant protein therapeutic or chemical compound. Several strategies are currently being investigated and include, cell therapies derived from autologous primary cell isolates, cell therapies derived from established cell lines, cell therapies derived from a variety of stem cells, including bone marrow/mesenchymal stem cells, cord blood stem cells, embryonic stem cells, as well as cells tissues and organs from genetically modified animals.
1. Autologous Cell Therapy
Tissue specific differentiated autologous cells (as opposed to autologous progenitor cells, see below) harvested from an individual, cultured ex vivo to expand, and reintroduced into a second site for repairing damaged tissue with "self" is ideal from an immunologic perspective. Several pre-clinical models as well as clinical applications are currently being explored and include chondrocytes for cartilage repair, keratinocytes and/or dermal fibroblasts for burn and wound repair, myocytes for myocardial repair, retinal pigment epithelial cells for age related macular degeneration and Schwann cell transplantation to restore myelin in CNS lesions.  The two most developed autologous cell therapies that have advanced from the laboratory to the clinic involve the repair of cartilage using autologous chondrocytes and the treatment of burns with autologous cultured keratinocytes.
Autologous progenitor cells harvested from an individual and used for "self" tissue repair is also immunologically ideal. The most widely used source of adult progenitor cells are derived from bone marrow.
Autologous peripheral blood or autologous bone marrow stem cells are currently used clinically.
2. Allogeneic Tissues and Cell Lines
The use of allogeneic tissue for transplantation is clinically routine due to the development of immunosuppressive drug therapies. The use of engineered tissue and specialized cell lines for the treatment of disease and injury is more recent and will also require immunosuppression unless engineering strategies are utilized to make the tissue resistant to immune destruction or through tissue processing to reduce immunogenicity. As is the case for autologous cell therapies, the furthest advances are in the area of connective tissue replacement, cartilage and skin. Currently, Apligraft® (Organogenesis, Inc) is used as a dermal replacement for chronic wounds and is composed of neonatal foreskin kerotinocytes and dermal fibroblasts. Although earlier studies demonstrated that Langerhan’s cell-free epidermal skin cultures were rejected following transplantation, Apligraft tissue appears to be uniquely non-immunogenic due to the processing of the tissue and represents an exception to the need for immunosuppression during allogeneic transplantation. A similar product, Dermagraft® is also available from Smith & Nephew.
Another interesting allogeneic cell type harvested from cadaveric sources for the treatment of Parkinson’s disease are allogeneic cultured retinal pigment epithelial cells that are encapsulated to provide an immune barrier.
3. Allogeneic stem cells
Allogeneic bone marrow transplantation is used clinically to treat hematologic disorders and cancer, but as is the case for autologous bone marrow transplantation, not from a commercial, tissue engineering standpoint. New clinical trials are focusing on the use of peripheral blood stem cells and specific subsets of bone marrow stem cells for these indications. The discovery and isolation of neural stem cells from fetal  and adult human brain is a significant development in the area of neural cell differentiation that has led to the possibility of producing specialized cells for the treatment of neurologic disorders, such as Parkinson’s disease and spinal cord injury.
Although stem cells from adult tissues have more plasticity than originally thought, they typically are limited in their capacity to generate all possible tissue and cell types. Stem cells derived from the inner cell mass of the early embryonic blastocyst (ES cells) can proliferate indefinitely and can give rise to virtually any cell type. The development of human embryonic stem cells has raised the possibility that an unlimited supply of human tissue could be generated from ES cells and that these tissues could be used to replace and repair damaged tissue in any organ system.
4. Xenotransplantation
In the ongoing search for a reliable source of tissue to replace lost cells, tissues and organs, research in the area of xenotransplantation (cross species transplantation) has grown tremendously in the last 20 years. Overcoming the immunologic hurdle of cross species transplantation as well as the problem of cross-species pathogen infectivity, i.e., xenozoonosis, are the scientific challenges facing the field. The ability to genetically modify species such as the pig through transgenesis and nuclear transfer, to express human genes and to mutate detrimental genes expressed in pig cells still holds promise for engineered tissues and organs for human transplantation. The production of galα1,3gal transferase null transgenic pigs  represents a significant development towards eliminating both hyperacute and acute vascular rejection and may lead to extended survival of pig organs in old world primates, including humans, in combination with standard triple drug immunosuppressive therapy.
Interestingly, there have been a series of pig-to-human xenotransplantation clinical experiments for the treatment of diabetes and FDA approved clinical trials for the treatment of neurologic disorders using outbred pig tissue. Although there was some evidence of cell engraftment in both indications, no efficacy was established due to the transplant. To date, a Phase I clinical trial was completed using transgenically engineered pig livers to detoxify the blood of fulminant hepatic failure (FHF) patients via extracoporial perfusion, however there is yet to be an FDA approved transgenic animal tissue for use in human transplantation.
Although the theoretical risk of xenozoonosis is a risk and represents a significant psychosocial issue, several studies investigating the possibility of cross species infectivity, including a retrospective analysis of 160 human transplant recipients exposed to porcine tissues have yet to reveal transmission of porcine viruses to humans or primates in vivo. The prospect of xenotransplantation is still relevant to solid organ and islet transplantation and with FDA oversight, animal as well as patient monitoring, the risks associated with xenozoonosis will be overcome.
Author: dragon web profit

Anti-Aging Skin Care Web Site: http://www.antiagingskincarebeauty.com

Emai: dragonwebprofit@antiagingskincarebeauty.com

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